0000000000294039
AUTHOR
Geethanjali Pickert
Wheat Consumption Aggravates Colitis in Mice via Amylase Trypsin Inhibitor–mediated Dysbiosis
Background & Aims Wheat has become the world's major staple and its consumption correlates with prevalence of noncommunicable disorders such as inflammatory bowel diseases. Amylase trypsin inhibitors (ATIs), a component of wheat, activate the intestine's innate immune response via toll-like receptor 4 (TLR4). We investigated the effects of wheat and ATIs on severity of colitis and fecal microbiota in mice. Methods C57BL/6 wild-type and Tlr4–/– mice were fed wheat- or ATI-containing diets or a wheat-free (control) diet and then given dextran sodium sulfate to induce colitis; we also studied Il10–/– mice, which develop spontaneous colitis. Changes in fecal bacteria were assessed by taxa-speci…
Nutritional Wheat Amylase-Trypsin Inhibitors Promote Intestinal Inflammation via Activation of Myeloid Cells.
Background & Aims Wheat amylase-trypsin inhibitors (ATIs) are nutritional activators of innate immunity, via activation of the toll-like receptor 4 (TLR4) on myeloid cells. We aimed to characterize the biologic activity of ATIs in various foods and their effect on intestinal inflammation. Methods We selected 38 different gluten-containing and gluten-free products, either unprocessed (such as wheat, rye, barley, quinoa, amaranth, soya, lentils, and rice) or processed (such as pizza, pasta, bread, and biscuits). ATIs were extracted and their biological activities determined in TLR4-responsive mouse and human cell lines. Effects of oral ATIs on intestinal inflammation were determined in health…
STAT3 links IL-22 signaling in intestinal epithelial cells to mucosal wound healing.
Signal transducer and activator of transcription (STAT) 3 is a pleiotropic transcription factor with important functions in cytokine signaling in a variety of tissues. However, the role of STAT3 in the intestinal epithelium is not well understood. We demonstrate that development of colonic inflammation is associated with the induction of STAT3 activity in intestinal epithelial cells (IECs). Studies in genetically engineered mice showed that epithelial STAT3 activation in dextran sodium sulfate colitis is dependent on interleukin (IL)-22 rather than IL-6. IL-22 was secreted by colonic CD11c+ cells in response to Toll-like receptor stimulation. Conditional knockout mice with an IEC-specific d…
Definitive evidence for Club cells as progenitors for mutantKras/Trp53‐deficient lung cancer
Accumulating evidence suggests that both the nature of oncogenic lesions and the cell-of-origin can strongly influence cancer histopathology, tumor aggressiveness and response to therapy. Although oncogenic Kras expression and loss of Trp53 tumor suppressor gene function have been demonstrated to initiate murine lung adenocarcinomas (LUADs) in alveolar type II (AT2) cells, clear evidence that Club cells, representing the second major subset of lung epithelial cells, can also act as cells-of-origin for LUAD is lacking. Equally, the exact anatomic location of Club cells that are susceptible to Kras transformation and the resulting tumor histotype remains to be established. Here, we provide de…
Non-celiac wheat sensitivity: differential diagnosis, triggers and implications.
Abstract Non allergy-non-celiac wheat sensitivity (NCWS) has become a common and often overrated diagnosis. Skepticism mainly relates to patients with prominent intestinal symptoms in the absence of general or intestinal signs of inflammation. There is consensus that the major wheat sensitivities, celiac disease and wheat allergy, have to be ruled out which may be difficult for wheat allergy. The non-inflammatory intolerances to carbohydrates, mainly lactose and FODMAPs (fermentable oligi-, di-, monosaccharides and polyols), which cause bloating or diarrhoea, can usually be excluded clinically or by simple tests. Recent studies and experimental data strongly indicate that NCWS exists in a s…
Activation of Intestinal Epithelial Stat3 Orchestrates Tissue Defense during Gastrointestinal Infection
Gastrointestinal infections with EHEC and EPEC are responsible for outbreaks of diarrheal diseases and represent a global health problem. Innate first-line-defense mechanisms such as production of mucus and antimicrobial peptides by intestinal epithelial cells are of utmost importance for host control of gastrointestinal infections. For the first time, we directly demonstrate a critical role for Stat3 activation in intestinal epithelial cells upon infection of mice with Citrobacter rodentium - a murine pathogen that mimics human infections with attaching and effacing Escherichia coli. C. rodentium induced transcription of IL-6 and IL-22 in gut samples of mice and was associated with activat…